The purpose of these studies are to evaluate the use of a rapid electron microscopic method (the pseudoreplica technique), combined with immune electron microscopy, for (1) the rapid diagnosis of congenital viral agents which might produce clinical manifestations in the neonatal period, or be subclinical but result in significant sequelae; (2) the detection of recognized or still uncharacterized viruses which might be involved in significant birth defects which affect at least 1% of all neonates. So far, this method has proven very specific for all cases of clinically manifest cytomegalovirus (CMV) or herpes simplex virus (HSV) infection and about two-thirds as sensitive as cultures for detecting subclinical cases of CMV. The technique has also been successfully adapted defects were diagnosed by electron microscopy by two new methods. Early diagnosis of congenital viral infections is proving to be valuable for potential preventive and therapeutic approaches and for prognostic considerations.